33 research outputs found
Thiazolamide-Ascorbic acid conjugate:a Îł-secretase inhibitor with enhanced blood-brain barrier permeation
International audienc
Simple coupling reaction between amino acids and weakly nucleophilic heteroaromatic amines
International audienc
Prospects for the resistance to HIV protease inhibitors: current drug design approaches and perspectives
International audienc
BACE-1 inhibitory activities of new substituted phenyl-piperazine coupled to various heterocycles: chromene, coumarin and quinoline
International audienc
Une Piste Pour Suivre La Transmission Glutamatergique Dans La Maladie Dâalzheimer
International audienc
Naphthyl and Coumarinyl Biarylpiperazine Derivatives as Highly Potent Human beta-Secretase Inhibitors. Design, Synthesis, and Enzymatic BACE-1 and Cell Assays.
International audienceTwenty novel Ăą-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinylseries were designed for their potential use in Alzheimerâs disease therapy. Enzymatic and cell-based assayshave been carried out. The biological results clearly demonstrate that specific substituents located at theN4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between40 and 70 nM). Variable temperature NMR and modeling studies are consistent with the obtained biologicaldata, since these studies confirmed that introduction at the N4-position of the piperazine ring allows productiveinteractions within the BACE-1 active site, which appear to be determinative for high BACE-1 inhibitoryactivity. These results are of particular interest since some of the new analogues belonging to the naphthylseries are almost one log more active than the best inhibitor of the similar family recently reported